This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The main objective of this project is to study the in vivo pathogenesis of different primary SIVsm lineages in rhesus macaques. Different strains of primary SIVsm lineages that have not undergone passage in rhesus macaques, display the viral diversity of different HIV-1 subtypes and may be significantly less virulent. Thus, infection of rhesus macaques with primary SIVsm isolates may better recapitulate the natural history of HIV infection, as compared to infection with pathogenic SIVmac239 infection. The SIV-specific immune response and its relation to the outcome of SIV infection in rhesus macaques infected with six different lineages of primary SIVsm isolates is being evaluated. These studies will provide insight into the viral and host determinants of disease progression to AIDS.